A total of 834 entries were obtained following search engine queries (PubMed: 381; ScienceDirect: 392; Cochrane Library Trials: 30 and ClinicalTrials.gov: 31). Table 2 summarises main limitations about the studies discussed. For these reasons, results should be interpreted with caution. These alterations easily lead to hyperandrogenism and irregular menstrual cycles. In addition, equol acts on incretins levels in endocrine L cell line GLUTag cells at concentration ranging from 50 to 300M, with long-term metabolic consequences(Reference Harada, Sada and Sakaguchi79). This phenomenon highlights how in literature there is greater attention to phytoestrogens and their effect, frequently underestimating the role of other components that have a marginal interest. These substances could play a role in the ovaries circulatory functions(Reference Oyawoye, Abdel Gadir and Garner50). Choose any of these varieties. In 2015, a longitudinal study found no differences in sexual organ development at 5 years of age between cow milk formula, breast milk and soy formula feeding(Reference Andres, Moore and Linam69). Even if serum AMH concentrations appear as a useful tool for predicting female fertility, only one study from our selection used them(Reference Haudum, Lindheim and Ascani46). The article processing charge was funded by the Baden-Wuerttemberg Ministry of Science, Research and Art and the University of Freiburg in the funding programme Open Access Publishing. Eating a few servings of soy each week could improve fertility and metabolic aspects of PCOS. These enzymes convert estrone and androstenedione into estrogen and testosterone(Reference Gunnarsson, Ahnstrm and Kirschner83,Reference Thompson and Siiteri84) . The interaction between isoflavones and ER estrogen receptor results in a competitive effect which in turn blunts endogenous estrogens action(Reference Rosselli, Reinhart and Imthurn72), as suggested by estrogenic activity of biochanin A and genistein on BT-474 human breast cancer(Reference Zand, Jenkins and Diamandis73). View all Google Scholar citations Moreover, two recent observational cohort studies by Chavarro and colleagues evaluated the association between soy consumption and in vitro fertilisation outcomes(Reference Vanegas, Afeiche and Gaskins40,Reference Chavarro, Mnguez-Alarcn and Chiu42) . Isoflavones are plant-based compounds found almost exclusively in beans, like soybeans, that mimic the action of the hormone estrogen. The two observational studies also show different limitations, in particular, one of these studies uses a follow-up of only 2 months. To put this into perspective, a 3.5-ounce (100-gram) serving of firm, calcium-set tofu offers about 60 mg of soy isoflavones, while 1 cup (240 mL) of soy milk contains only about 28 mg. Soy consumption is supposed to have protective effects against cardiovascular disease by cholesterol-lowering and blood pressure improvement action and in the prevention of cancer or diabetes and it also supports bone health and the management of menopause symptoms(Reference Ding, Pan and Manson2Reference Mosallanezhad, Mahmoodi and Ranjbar8). It helps you to ovulate and they quality. Participants were classified by ethnicity; however, the population sample size did not allow to perform stratification of outcomes based on this aspect. Progesterone and sex hormone-binding globulin (SHGB) levels were not significantly changed by soy intake. Soy consumption was not related to estradiol levels or endometrial thickness. Table 1. However, stratification for the control group or PCOS patients did not show a significant correlation between androgens and equol production. 3 Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy. Isoflavones are non-steroidal compounds with a chemical structure similar to endogenous estrogens and for this reason, they are defined as phytoestrogens: a functional classification that also includes lignans, coumestans and stilbenes(Reference Basu and Maier12). The concomitant treatment with soybean phytoestrogens significantly increased the implantation rate (254% v. 202%; P<005), the pregnancy rate (393% v. 209%; P<005) and the pregnancy-to-delivery rate (303% v. 162%; P<005) compared with placebo. Interest in soy is particularly driven by its possible beneficial effects on human health. Get company information for Twins Club, Inc. in RANCHO CUCAMONGA, CA. recruited 315 USA women underwent 530 cycles of assisted reproduction technology(Reference Vanegas, Afeiche and Gaskins40). Close this message to accept cookies or find out how to manage your cookie settings. However, after removing data from studies with elevated bias risk, three studies were included in the sensitivity analysis with consequent loss of statistical significance. Uses. Romualdi and colleagues in 2008 enrolled twelve Italian women with metabolic syndrome and PCOS and with a follow-up of 6 months using 36mg/d of oral genistein as an intervention(Reference Romualdi, Costantini and Campagna34). Although not strictly related to the aspect of fertility, the study is still ongoing (Clinicaltrials.gov: NCT00616395) intending to follow the participants to evaluate effects on reproductive functions, later in life. Furthermore, the evaluation of dietary pattern before infertility treatments does not exclude the possibility that soy consumption may have been influenced by the search for a healthy pattern to achieve pregnancy. Render date: 2023-03-02T11:20:28.481Z WHAT IS IT? They evaluated the hormonal variations during menstrual cycle through the composite construct that considered the cumulative information of the day of menstrual cycle for specimens. Additionally, isoflavones can act as antioxidants in vitro (15), but the extent to which they contribute to the antioxidant status of humans is not yet clear. However, even in the West, it is currently widely used, especially due to its versatility in plant-based products for health purposes and vegetarian diets(Reference Rizzo and Baroni1). The detailed selection process is highlighted in Fig. CA. Microbial alpha diversity and glucose homeostasis improved in PCOS group after isoflavone intervention, resembling the control group profile at baseline. Conclusions: These data suggest that higher intake of soy foods and soy isoflavones is associated with lower sperm concentration. (As part of this process, a group of eggs matures so that one will be ready for release during ovulation .) However, urinary phytoestrogen levels were only detected at baseline and this increased the correlation uncertainty. Furthermore, it should be considered that, as already discussed, many studies display several limitations including inadequate sampling of hormone concentrations during all phases of cycle, low number of participants and the lack of a placebo group. The present study used a community-based approach with recruitment of couples seeking pregnancy. From obtained data, it seems likely that soy consumption, not only in the form of isoflavones in pharmacological quantities, could have a beneficial effect on fertility, especially in those individuals with fertility problems. Soy food and soy isoflavone intake were unrelated to sperm motility, sperm morphology or ejaculate volume. Adapted from Moher et al.(24). Metabolic, endocrine, inflammation, and oxidative stress . Multiple regression analysis including various set of possible confounders highlighted more in-depth correlations. The authors found an association between pregnancy outcomes and urinary Bisphenol A (BPA), dependent on soy consumption in the multivariable-adjusted mixed model. Adapted from SMART: Servier Medical Art(89). Journal of Clinical Endocrinology and Metabolism randomized 70 women with PCOS into two groups to take either 50 mg/d soy isoflavones or a placebo for 12 weeks. M. L. contributed to drafting and revising the manuscript. Find company research, competitor information, contact details & financial data for Lucky Twins Distribution of Rancho Cucamonga, CA. Despite the 6-month duration of the clinical trial, the lack of a placebo group, the absence of characterisation of equol-competence among individuals and the limited number of participants reduced the strength of the results obtained. Furthermore, the nutritional habits of Adventists differ from the Western population ones and they show soy consumption more similar to populations in South-East Asia(Reference Messina53). From the sub-analysis by ethnic stratification, follicular SHBG levels were higher in non-Asians. If we eat soy, do we keep the beneficial effects of the Mediterranean diet? Flowchart for studies selection. In the first study, the authors administered soy milk to six American women aged 2229 for 1 month, comparing outcomes with baseline(Reference Lu, Anderson and Grady26). The dietary intake of isoflavones did not appear to be associated with fertility in the two cohorts but some marginal evidence of amelioration of fertility was related to a higher intake of isoflavones among 30 years old individuals after age stratification (Fecundability Ratios: 112, 95% CI 994, 134 and 119, 95% CI 092, 155 in the two cohorts comparing 90th with <24th percentile). The procedure was carried out following the most recent PRISMA guidelines(Reference Liberati, Altman and Tetzlaff23). Moreover, isoflavones act as selective estrogen receptor modulators (SERMs) showing both agonist and antagonist effects on ER, with subsequent estrogenic, anti-estrogenic or even neutral effects(Reference Liu, Li and Chen14). The obtained meta-analysis was included in the final summary because it assessed aspects relating to the topic of this review. The possible correlation between menstrual cycle length and soy does not seem convincing either. It would have been useful to have retrospective information on soy consumption to assess the potential effect on previous fertility problems. In particular, soy contains numerous non-isoflavone constituents such as phytic acid, triterpenes and sterols, BowmanBirk protease inhibitors, unsaturated fatty acids, saponins, inositol phosphates, proteins, peptides such as lunasin;(Reference Kang, Badger and Ronis10) nevertheless, soy isoflavones have attracted much attention in the last years for its estrogenic as well as non-hormonal properties(Reference Aulisa, Binda and Padua11). Individuals who are not equol-producers have likely limited response to isoflavone intake(Reference Iino, Shimoyama and Iino16). Phytoestrogens and breast cancer promoters or protectors? It is plausible that isoflavones bind to this blood carrier and stimulate its hepatic synthesis. Therefore, the lack of fecundity is called sterility(Reference Wood47). Additionally, the enrolment criteria included only women who had stopped oral contraception less than 2 months earlier, so highly fertile individuals could have been excluded. Although this clinical trial showed the long-term effect of soy ingestion on serum hormone levels, it was a pilot study with a limited number of participants (fourteen premenopausal women). The duration of menstrual cycle, especially in luteal phase, can also have a direct influence on the mammary gland proliferation, through a reduction in exposure of the epithelium to proliferative hormones. Pending further confirmation, soy and its components do not appear to have a clinically relevant influence on menstrual cycle in healthy women. The Adventist Church is a community with very homogeneous habits and a high prevalence of vegetarians (54% lacto-ovo vegetarian and 7% vegan from this study)(Reference Kent, Morton and Ward51,Reference McBride, Bailey and Landless52) . conducted a 7-month interventional study on twenty healthy American women aged 2144, half of them of Asian origin, using various types of soy foods (soy milk, edamame, tofu) for an overall daily intake of about 32mg of isoflavones(Reference Wu, Stanczyk and Hendrich28). 2. Among selected prospective cohort studies, in 2012 Jarrell and colleagues conducted an observational study of 323 Canadian women with late pregnancy (aged at least 35) followed from the second month of pregnancy until delivery(Reference Jarrell, Foster and Kinniburgh36). Among the limitations of this review of literature, we must include the possible avoidance of studies that considered fertility as a secondary outcome and which therefore may have escaped from the manuscript selection. However, the intakes of isoflavones in the studied cohorts were limited (range: 0331mg/d). Additional considerations regarding hormonal influences will be discussed in the next paragraph. There was a significant correlation between dietary soy consumption and fertilisation rate (77% v. 71%, P=0004), age-adjusted pregnancy (52% v. 41%, P=003) or age-adjusted live birth rate (44% v. 31%, P=0007) among soy consumers compared with non-consumers. Four clinical trials were found among search engines results: two longitudinal pilot studies(Reference Romualdi, Costantini and Campagna34,Reference Haudum, Lindheim and Ascani46) and two interventional studies with a parallel design, both conducted in Iranian populations(Reference Khani, Mehrabian and Khalesi35,Reference Jamilian and Asemi43) . Soybeans are the most common source of isoflavones in human food; the major isoflavones in soybean are genistein and daidzein. It is widely used in eastern traditional cuisine and it has recently diffused among self-conscious and vegetarian diets. Soya Isoflavones and Vitamins The Group for those Using, Abusing and thinking about taking over the counter items to boost fertility. The authors of this recent literature review of available evidence from observational and interventional studies concluded that soy and its components cannot be classified as an endocrine disruptor. The length of menstrual cycle may represent an indirect marker of ovarian function and reproductive health(Reference Mumford, Steiner and Pollack54,Reference Vassena, Vidal and Coll55) . Consequently, the absence of fertility, called infertility, is a disease characterised by the failure to establish a clinical pregnancy and it can depend on various factors including predisposition and behavioural/environmental aspects. The effects of phytoestrogen genistein on steroidogenesis and estrogen receptor expression in porcine granulosa cells of large follicles, Endocrine-disrupting chemicals as modulators of sex steroid synthesis, Amplification of HSD17B1 and ERBB2 in primary breast cancer, Utilization of oxygen and reduced nicotinamide adenine dinucleotide phosphate by human placental microsomes during aromatization of androstenedione, Genistein is an effective stimulator of sex hormone-binding globulin production in hepatocarcinoma human liver cancer cells and suppresses proliferation of these cells in culture, Xenoestrogen interaction with human sex hormone-binding globulin (hSHBG), Inhibition of tumor promoter-induced hydrogen peroxide formation in vitro and in vivo by genistein, Phytoestrogen concentrations in serum from Japanese men and women over forty years of age, Neither soyfoods nor isoflavones warrant classification as endocrine disruptors: a technical review of the observational and clinical data, Flowchart for studies selection. In two studies, women having fertility treatment took part in research looking at the amount of soya they ate, and whether that affected the success of their treatment. Smaoui, Slim Measurement of urinary isoflavones and their metabolites appears to be a more reliable approach than dietary assessment alone. This may have influenced the presence of large confidence intervals. Clinical trials can provide solid causal inferences, but they often have limitations in terms of study duration or intervention design. (Reference Filiberto, Mumford and Pollack37). Furthermore, the intervention group showed lower rates of miscarriage (n: 2, 31% v. n: 6, 87%; P<005) and higher rates of pregnancy (n: 13, 200% v. n: 3, 44%; P<005) compared with placebo. This effect persisted for at least one menstrual cycle after the suspension of soy intake, with a maximum of persistence for three menstrual cycles. As for males, a 2010 meta-analysis highlighted the safety of soy on fertility outcomes(Reference Hamilton-Reeves, Vazquez and Duval21), recently confirmed by an updated meta-analysis on this topic(Reference Reed, Camargo and Hamilton-Reeves22). The soy isoflavones block the estrogen receptors in your brain and fool your body into thinking its natural estrogen levels are low. for this article. However, among fertile individuals, it may have a neutral effect, as discussed in the previous paragraphs. In the first clinical trial by Unifer and colleagues, 1500mg/d of isoflavones from soy or placebo were administered for 10d to 134 women who had been infertile for at least 2 years, undergoing intrauterine insemination after 100mg/d for 5d of clomiphene citrate treatments (an ovulation inducer)(Reference Unfer, Casini and Costabile31). Studies have also shown that soybeans contribute towards lower levels of cholesterol, less risk of heart disease, breast cancer, and osteoporosis and fewer menopausal symptoms. In addition, non-English papers could have provided relevant data on the topic, especially those from countries with a more consistent history of soy consumption. 2022. Concerns that the phytoestrogens (isoflavones) in soy may feminize men continue to be raised. Isoflavones concentrations did not show significant differences between participants at baseline. DOI: 10.1017/jns.2022.15. The authors wish to thank Sandra De Dominici for language revision assistance. The same amount of genistein was used in a parallel clinical trial on 137 Iranian women with PCOS with a 3-month follow-up(Reference Khani, Mehrabian and Khalesi35). The authors highlighted a marginal reduction of luteal phase in the adjusted multivariable model for an increase of 10mg/d of dietary isoflavones (aOR: 138, 95% CI 099, 192, P=006), identified by monitoring LH levels in urine by a fertility monitor and 4-d per cycle 24-h dietary recalls. 1 The FDA based this decision on clinical studies showing that at least 25 g of soy protein per day lowered . Only 6% of participants had not soy isoflavone intake. However, even in the West, it is currently widely used, especially due to its versatility in plant-based products for health purposes and vegetarian diets (Reference Rizzo and Baroni 1).Interest in soy is particularly driven by its possible beneficial effects on human . Previously, Petrakis and colleagues proposed an interventional study with a soy isolate (374g of soy protein containing 374mg of genistein) on twenty-four women (pre- and post-menopause) followed for 6 months plus 3 months pre-intervention and 3 months post-washout(Reference Petrakis, Barnes and King25). The evaluation at two different times of menstrual cycle allowed to discriminate the effect between luteal and follicular phases but not day by day hormonal fluctuations. The authors found no significant differences in reproductive outcomes (missed menstrual periods, pregnancy, live births, abortions, miscarriages, full-term deliveries, preterm deliveries, etc.) Li, Hang For this reason, they are classified as phytoestrogensplant-derived compounds with estrogenic activity (1). After the intervention period, four patients became pregnant and twelve patients showed ovulation improvements based on ultrasonography (P<005). The consumption of soy over time, the possible use of certain foods considered healthy in seeking pregnancy or the willingness to avoid pregnancy could generate spurious associations. In addition, full-text bibliographic lists from selected papers were screened to retrieve further relevant articles. Most women taking soy isoflavones to induce ovulation take around 150-200 mg a day on cycle day 3 -7 or 5-9. Results from a pilot study, Effect of soy phytoestrogen on metabolic and hormonal disturbance of women with polycystic ovary syndrome, Usual dietary isoflavone intake and reproductive function across the menstrual cycle, Soy isoflavone intake and the likelihood of ever becoming a mother: the adventist health study-2, Higher urinary lignan concentrations in women but not men are positively associated with shorter time to pregnancy, Soy food intake and treatment outcomes of women undergoing assisted reproductive technology, Dietary factors and luteal phase deficiency in healthy eumenorrheic women, Soy intake modifies the relation between urinary bisphenol A concentrations and pregnancy outcomes among women undergoing assisted reproduction, The effects of soy isoflavones on metabolic status of patients with polycystic ovary syndrome, Dietary phytoestrogen intakes of adult women are not strongly related to fecundability in 2 preconception cohort studies, Urinary phytoestrogens and relationship to menstrual cycle length and variability among healthy, eumenorrheic women, Impact of short-term isoflavone intervention in polycystic ovary syndrome (PCOS) patients on microbiota composition and metagenomics, Fecundity and natural fertility in humans, Isolation and determination of anthocyanins in seed coats of black soybean (, Antioxidants and reactive oxygen species in follicular fluid of women undergoing IVF: relationship to outcome, The influence of religious affiliation on participant responsiveness to the complete health improvement program (CHIP) lifestyle intervention, Health beliefs, behavior, spiritual growth, and salvation in a global population of seventh-day adventists, A brief historical overview of the past two decades of soy and isoflavone research, The utility of menstrual cycle length as an indicator of cumulative hormonal exposure, Menstrual cycle length in reproductive age women is an indicator of oocyte quality and a candidate marker of ovarian reserve, Prospective evaluation of luteal phase length and natural fertility, Menstrual cycle characteristics and fecundability in a North American preconception cohort, A prospective cohort study of menstrual characteristics and time to pregnancy, Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women: a systematic review and meta-analysis, Hormonal effects of soy in premenopausal women and men, Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature, Dysbiosis of gut microbiota associated with clinical parameters in polycystic ovary syndrome, The (TAAAA)n microsatellite polymorphism in the SHBG gene influences serum SHBG levels in women with polycystic ovary syndrome, Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis, Dietary patterns and outcomes of assisted reproduction, Compared with feeding infants breast milk or cow-milk formula, soy formula feeding does not affect subsequent reproductive organ size at 5 years of age, Early-life soy exposure and age at menarche, Consumption of soy-based infant formula is not associated with early onset of puberty, Cellular and biochemical mechanisms by which environmental oestrogens influence reproductive function, Steroid hormone activity of flavonoids and related compounds, Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta, Rapid endocrine disruption: Environmental estrogen actions triggered outside the nucleus, Equol-stimulated mitochondrial reactive oxygen species activate endothelial nitric oxide synthase and redox signaling in endothelial cells: roles for F-actin and GPR30, Genistein, a specific inhibitor of tyrosine-specific protein kinases, Estradiol or genistein prevent Alzheimer's disease-associated inflammation correlating with an increase PPAR gamma expression in cultured astrocytes, Bacterial metabolite S-equol modulates glucagon-like peptide-1 secretion from enteroendocrine L cell line GLUTag cells via actin polymerization. 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